This invention relates to the determination of drugs of abuse. In some embodiments the invention relates to enhancing detection of adulterants that may be present in a biological sample to be tested for drugs of abuse.
As the use of illicit drugs has increased, public concern over the problems associated with its effects has grown. Drug use is generally recognized as a significant contributory factor in the current rise of accidents. Employers, government organizations, and others are increasingly using drug screening and freedom from drugs as conditions of employment. This concern has led to workplace drug testing in order to identify, treat, and remove active drug users from the workforce. Initial drug testing in the workplace revealed the obtrusive incursion of drug use and abuse in the daily lives of a significant portion of Americans. Further research indicated the staggering costs to public and private industry in terms of lost productivity, increased health care costs, and human suffering and death due to drug abuse. As a result, drug testing has spread to all areas of the public and private sector.
Because of the above, individuals may be requested or required to provide a sample such as a urine sample that will be tested for the presence of drugs of abuse or metabolites of drugs of abuse. An initial or screening test is frequently performed first. A positive result is usually confirmed by a method different from that used for initial testing, which usually has greater sensitivity and specificity than the initial test. An initial negative test, however, is usually not confirmed. Thus, an individual who is fearful of a positive result in an initial screening test may alter his or her urine sample to prevent detection of the drug or drug metabolite.
Many screening tests utilize antibody-antigen reactions quantified by means of an enzyme indicator. The confirmation assays, on the other hand, are labor and time intensive, highly accurate, expensive, and more difficult to adulterate. In addition, the positive screen has already raised a red flag, thereby drawing attention to the sample. The confirmation analysis utilizes GC-MS (gas chromatography mass spectrometry) testing which is considered the “gold standard” for drug assays scientifically and legally.
One method of altering a urine sample is by diluting the sample so that the drug or drug metabolite concentration is below the detection threshold in a screening test. For example, water and/or saline may be added to the sample to dilute the drug or its metabolite to a concentration that is less readily detected by the screening test. To detect this type of alteration, the urine sample is frequently assayed to determine if physiological parameters such as creatinine concentration, pH, and specific gravity are within normal ranges, or if these parameters are abnormal due to the presence of diluent.
Chemical adulterants may be added to a sample in an attempt to produce a false negative result in the initial screening test. In some instances, the chemical adulterants chemically convert a drug or a drug metabolite to a less detectable or non-detectable product. Adulteration techniques can be divided into two distinct types. The first utilizes an “in vivo” technique in which the user consumes the adulterant. The second technique utilizes an “in vitro” method in which the abuser adds the adulterant directly to the urine specimen submitted for testing.
In vitro methods utilize numerous products and compounds that will adversely affect either the screening or confirmation process. Products affecting the screening process include many household products and also commercially available products sold for the purpose of obscuring the result of a drug test. These products include oxidants such as, for example, hydrogen peroxide, sodium nitrite, bromates such as, e.g., sodium bromate, potassium bromate, etc., bromine, bleach (sodium hypochlorite), chromates such as, e.g., pyridinium chlorochromate, etc., nitrites, iodine, iodate, iodic acid, periodate, and the like.
The presence of chemical adulterants is more difficult to assess, since tests for the specific chemicals must be performed. As each new chemical adulterant is recognized and identified, tests are developed for identification of the specific adulterant. However, with the development of multiple adulterants, each of which is chemically distinct and each of which is capable of destroying or masking drugs of abuse or their metabolites, the process of identifying adulterated urine samples becomes increasingly difficult. Multiple tests must be performed on each sample to assure detection of all chemically adulterated samples. Furthermore, there is a period of time for each adulterant during which samples containing that adulterant are not detected because the test-specific adulterant has not yet been identified and/or confirmed.
Sample adulteration can affect many of the commonly used methods for detection of drugs of abuse including, for example, enzyme immunoassay (EMIT or EIA), radioimmunoassay (RIA), and florescent polarization immunoassay (FPIA) and so forth. Consequently, clinical chemistry literature recommends, and SAMSHA Mandatory Guidelines for Federal Workplace Drug Testing Programs now require, that testing for drugs of abuse in urine samples include testing for adulterants to identify urine samples that have been adulterated.
Various compositions and methods have been developed to detect one or more of a group of adulterants that are added to biological samples such as urine to prevent detection of drugs of abuse. Examples of such compositions include chromophoric agents such as, for example, 3,3′,5,5′-tetramethylbenzidine, diaminobenzidine, 3-amino-9-ethylcarbazone, 4-chloro-1-napthol, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid, ortho-phenylene-diamine, and so forth.
There is a need for enhancing detection of adulterants in samples for analysis of drugs of abuse. In particular, there is a need for increasing sensitivity of compositions used for detection of adulterants. The enhanced detection of adulterants should be realized for both manual and automatic processes.